|Title||Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region|
|Publication Type||Journal Article|
|Year of Publication||2005|
|Authors||Pufall, MA, Lee, GM, Nelson, ML, Kang, HS, Velyvis, A, Kay, LE, McIntosh, LP, Graves, BJ|
|Type of Article||Article|
|Keywords||allosteric regulation, AUTOINHIBITION, DOMAIN, DYNAMICS, NMR-SPECTROSCOPY, PHOSPHORYLATION, PROTEIN, SITES, TRANSACTIVATION, TRANSCRIPTION FACTOR NFAT1|
Cell signaling that culminates in posttranslational modifications directs protein activity. Here we report how multiple Ca2+-dependent phosphorylation sites within the transcription activator Ets-1 act additively to produce graded DNA binding affinity. Nuclear magnetic resonance spectroscopic analyses show that phosphorylation shifts Ets-1 from a dynamic conformation poised to bind DNA to a well-folded inhibited state. These phosphates lie in an unstructured flexible region that functions as the allosteric effector of autoinhibition. Variable phosphorylation thus serves as a "rheostat" for cell signaling to fine-tune transcription at the level of DNA binding.
|URL||<Go to ISI>://000230212800079|